The invention relates to prostaglandin E1 derivatives (PGE1 derivatives) as pharmacologically active agents and to pharmaceutical compositions--especially for transcutaneous (transdermal) application--which contain a PGE1 derivative.
DE-A-27 53 986 and the corresponding U.S. patent application No. 4,205,178 disclose 6-keto prostaglandin E1 derivatives, especially the 6-keto PGE1 methyl ester.
A number of biological and pharmacological effects are described for these compounds. Various routes of administration are indicated for the various kinds of illnesses to be treated, e.g. oral, intravenous, subcutaneous, intra-arterial, buccal, rectal and intra-vaginal administration. Topical administration is described in connection with skin injuries or skin diseases at or near the site of the injury or disease.
6-keto prostaglandin E1 derivatives are also described in DE-A-28 40 032, in which the authors also refer to various forms of pharmacological activity and administration.
Prostaglandin E1 (PGE1) and 6-keto prostaglandin E1 (6-k PGE1) can be used for the treatment of several diseases. These diseases include peripheral occlusive diseases, complications in arteriosclerosis such as Meniere's disease or acute loss of hearing, acute myocardial infarctation, unstable angina pectoris, acute ischaemic strokes, impotence, bronchial asthma, impaired hair growth and rejection following kidney transplants; see H. Sinzinger and W. Rogatti, Prostaglandin E1 in atherosclerosis, Springer Verlag Berlin--Heidelberg--New York, 1986; S. Schrey, PGE1, Therapie der arteriellen Verschlusskrankheit, Universitatsdruckerei and Verlag Dr. C. Wolf und Sohn, Munich, 1985. PGE1 is used for the treatment of chronic arterial occlusive diseases in phase III and IV. This condition calls for intra-arterial or intravenous infusion which results in a severe limitation in the use of PGE1, as the infusion is not only a strain on the patient, but also involves a certain risk of arterial haemorrhage. Neither route of administration (i.a. and i.v.) is suitable for continuous therapy in ambulatory patient care. However, long-term administration would be most appropriate for these diseases. The oral administration of PGE1 is always problematic as either the very low bio-availability rules out such administration, or the typical undesired effects (nausea, vomiting, diarrhoea) are prohibitive due to the high concentration of the drug in the gastrointestinal tract when orally administered.